A Study in Advanced/Metastatic Solid Tumors With the Study Medicine (PF-07329640) When Given Alone or In Combination

Colorectal Cancer Clinical Trial

— LTbR  

Official title:

FIRST-IN-HUMAN (FIH), OPEN-LABEL, PHASE 1 DOSE ESCALATION AND EXPANSION STUDY DESIGNED TO EVALUATE THE SAFETY, TOLERABILITY, PK, PD, AND PRELIMINARY CLINICAL ACTIVITY OF PF-07329640 AS A SINGLE AGENT OR IN COMBINATION TREATMENT FOR PARTICIPANTS WITH ADVANCED SOLID TUMORS.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06448364
• Other study ID #: C5181001
• Status: Recruiting
• Phase: Phase 1
• Start date: May 9, 2024
• Est. completion date: January 1, 2029

Study information

• Verified date: June 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to learn about the safety (the impact of the study drug on the participant's body), effects of the study drug alone or in combination with bevacizumab or sasanlimab, and to find the best dose.

This study is seeking participants who have solid tumors that:

• have advanced (cancer that doesn't disappear or stay away with treatment) or

• has spread to other parts of the body (metastatic).

This includes (but limited to) the following cancer types:

• Non-Small Cell Lung Cancer (NSCLC): It's a type of lung cancer where the cells grow slowly but often spread to other parts of the body.

• Colorectal Cancer (CRC): This is a disease where cells in the colon or rectum grow out of control.

• Urothelial Cancer (UC): This is a cancer that starts in the urinary systems.

• Melanoma: Skin cancer that develops when melanocytes (the cells that give the skin its tan or brown color) start to grow out of control.

All participants in this study will receive the study medication (PF-07329640) as an IV infusion (given directly into a vein) at the study clinic every week for repeating 28-day cycles.

Depending on which part of the study participants are enrolled in they will receive the study medication (PF-07329640 alone or in combination with other anti-cancer medications (bevacizumab or sasanlimab). Bevacizumab is given in the clinic as IV infusion every two weeks and sasanlimab is given as a shot under the skin every 4 weeks.

Participants can continue to take the study medication (PF-07329640) and bevacizumab until their cancer is no longer responding. Participants who are taking sasanlimab may receive it for up to 2 years.

The study will look at the experiences of people receiving the study medicines. This will help see if the study medicines are safe and effective.

Participants will be involved in this study for up to 4 years. During this time, they will have a study visit every week. After they have stopped taking the study medication (at about at 2 years) they will be followed for another two years to see how they are doing.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: January 1, 2029
• Est. primary completion date: January 2, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histological or cytological diagnosis of advanced, unresectable, and/or metastatic or relapsed/refractory solid tumor

• Part 1:

• Part 1A: Participants with solid tumors where anti-PD-(L)1 is an established treatment. Participants must have progressed on or following prior anti-PD-(L)1 therapy if approved, available, tolerable, and eligible.

• Part 1B & C: Participants either meeting Part 1A criterion, or participants with "cold" solid tumors where anti-PD-(L)1 therapy is not an established treatment

• Part 2:

• Part 2A:

• Cohort 1: Participants with NSCLC must have received platinum-based chemotherapy and anti-PD-(L)1 or have intolerability to or refusal of standard therapies. NSCLC participants with known activating mutation(s) must also have received prior approved and available targeted therapy(ies) for the associated mutation(s) or have intolerability or documented refusal of these therapies.

• Cohort 2: Participants with MSS CRC must have received at least fluoropyrimidine-, oxaliplatin, and irinotecan-based chemotherapy, an anti-VEGF agent (if not receiving anti-VEGF on protocol), and anti-epidermal growth factor receptor (EGFR) inhibitor (if RAS wildtype) and/or other molecularly targeted therapy if appropriate.

• Part 2B:

• NSCLC (2L+) participants as described above in Part 2A

• MSS CRC (2L+) participants as described above in Part 2A

• UC (2L+) participants must have received prior platinum-based chemotherapy, anti-PD-(L)1 therapy, or enfortumab vedotin.

• Part 2C; anti-PDx naive NSCLC (1L) participants must not have received standard of care therapy with anti-PD-(L)1.

• At least 1 measurable lesion based on RECIST 1.1 that has not been previously irradiated (Part 1 exceptions permitted after review and approval)

• Able to provide pre-treatment (and optional on-treatment) tumor tissue

• Resolution of acute effects of any prior therapy to either baseline or CTCAE Grade 1

Exclusion Criteria:

• Treatment with any systemic anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to planned first dose

• Prior treatment with another anti-LTßR agonist

• Systemic anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to planned first dose (6 weeks for mitomycin C or nitrosoureas). Prior targeted or endocrine therapy require an interval of 2 weeks or 5 half-lives (whichever is shorter) prior to planned first dose.

• Lack of adequate organ (bone marrow, renal, liver) function

• Active infection requiring systemic treatment.

• Active or history of autoimmune disease (eg, systemic lupus erythematosus, rheumatoid arthritis) requiring chronic systemic steroid or immune-modulatory therapy (not including oral physiological replacements)

• History of Grade =3 immune mediated adverse event (AE) (including aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevations that were considered drug related) and/or CRS that was considered related to prior immune-modulatory therapy and required immunosuppressive therapy.

• Known or suspected hypersensitivity to any PF-07329640 components, or to monoclonal antibodies (mAbs) or other therapeutic proteins such as fresh frozen plasma, human serum albumin, cytokines, or interleukin, or anti-PD-(L)1 therapy (the latter applicable for Part 1C and Part 2B/C participants only

• Brain metastasis or primary brain tumor requiring immediate local intervention (surgery, radiosurgery) in the opinion of the investigator.

• Other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix, Bowen's disease. Presence of other indolent cancer requires prior sponsor approval.

• Organ transplant requiring immunosuppressive treatment or prior allogeneic bone marrow or hematopoietic stem cell transplant.

• Pregnant or breastfeeding

• Persistent or recurring = Grade 2 neuropathy prior to study entry

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumors
• Carcinoma, Non-Small-Cell Lung
• Colorectal Cancer
• Colorectal Neoplasms
• Lung Neoplasms
• Melanoma
• Non-Small Cell Lung Cancer
• Urothelial Cancer

Intervention

Biological:
• PF-07329640
an anti-lymphotoxin beta receptor agonist
• sasanlimab
A monoclonal antibody that blocks the interaction between PD-1 and PD-L1/L2
• bevacizumab
a monoclonal antibody that blocks VEGF

Locations

Country	Name	City	State
Puerto Rico	Hospital Oncológico Dr. Isaac González-Martinez	Rio Piedras
Puerto Rico	Pan American Center for Oncology Trials, LLC	Rio Piedras
Puerto Rico	Pan American Center for Oncology Trials- Hospital Oncologico	Rio Piedras
United States	NEXT Oncology	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PART 1: Number of participants with Dose-limiting toxicities (DLT)	Any of the prespecified AEs that are attributable to one, the other, or both study treatments, occurring in the DLT observation period are considered DLTs, excluding toxicities clearly due to underlying disease or extraneous causes:	First cycle, Day 1 up to Day 28
Primary	PART 1 & 2: Incidence of Adverse Events (AE)s	An adverse event (AE) was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. AEs included both serious and all non-serious AEs.	From start of the treatment up to 90 days after last dose or start of new anticancer therapy, whichever occurred first
Primary	To: PART 1 & 2: Number of participants with laboratory abnormalities	Number of participants with laboratory test abnormalities. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick and microscopy).	From start of treatment up to 90 days after last dose or start of new anticancer therapy, whichever occurred first
Primary	Part 2: "Objective Response - Number of Participants With Objective Response "	Percentage of participants with objective response-based best overall response (BOR) of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by the Investigator.	Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years'
Secondary	Part 1: Objective Response - Number of Participants With Objective Response	Percentage of participants with objective response-based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by the Investigator	Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years
Secondary	Time to event endpoints: duration of response (DOR) by RECIST v1.1	Time to event: DOR according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as assessed by the Investigator.	Baseline to confirmed disease progression, up to 2 years after the last dose of study treatment
Secondary	Time to event endpoints: progression-free survival (PFS) by RECIST v1.1	Time to event: PFS according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as assessed by the Investigator.	Baseline to confirmed disease progression, up to 2 years after the last dose of study treatment
Secondary	Part 1A: Maximum Observed Serum Concentration (Cmax) of PF-07329640	Cycle 1: Pre-dose, End of Infusion (EOI), 4, and 8 hours Cycle 2: Pre-dose, EOI, 4, and 8 hours	Cycle 1 Day 1 & Cycle 2 Day 1 (each cycle is 28 days)
Secondary	Part 1A: Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-07329640	Cycle 1: Pre-dose, End of Infusion (EOI), 4, and 8 hours Cycle 2: Pre-dose, EOI, 4, and 8 hours	Cycle 1 Day 1 & Cycle 2 Day 1 (each cycle is 28 days)
Secondary	Part 1A: Serum Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07329640	Cycle 1: Pre-dose, End of Infusion (EOI), 4, 8, 24, 48, 72 hours post-dose (Day 1-4); Pre-dose, EOI, 4 hours post-dose (Day 8); pre-dose, EOI (Day 15) Cycle 2: Pre-dose, EOI, 4, 8, 24, 48, 72 hours post-dose (Day 1-4); Pre-dose, and 4 hours post-dose (Day 15)	Cycle 1 Day 1 & Cycle 2 Day 1 (each cycle is 28 days)
Secondary	Serum Concentrations of PF-07329640 in combination (Part 1B/1C/2A/2B/2C)	comparison Predose and end of infusion blood serum concentrations at Cycle 1 day 1 and 15, and Cycle Day 1	pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1Day 15, Cycle 2 Day 1 (Each cycle is 28 days)
Secondary	Incidence and titers of antidrug antibodies (ADA) against PF-07329640	the number of patients with ADAs against PF-07329640 and the concentration of those ADAs	Baseline though study completion, an average of 2 years
Secondary	Paired Tumor Biopsies	Changes in quantity and maturation state of tertiary lymphoid structure (TLS)s in tumor biopsy tissues at Cycle 2 Day 15	Baseline through Cycle 2 Day 15 (each cycle is 28 days)

External Links

•   To obtain contact information for a study center near you, click here.